1. Field of the Invention
The present invention relates in general to electrotherapy devices and more particularly to devices and methods for photodynamic stimulation of living tissue, directly and also indirectly by stimulation of photosensitive substances introduced into or onto living tissue.
2. Description of the Related Art
Mitochondria within cells of protozoa and metazoa represent sources of energy delivering vesicular respiration. They are moreover capable of synthesizing proteins, because they dispose from the cell nucleus an independent or self-dependent genetic system of DNA and RNA.
The mitochondria's main function however is vesicular respiration, that is within the cells the transformation of nutrient media and oxygen either supplied through the blood stream or in some other way into energy and endogenous substances, whereby through this transformation, waste products like water, carbon dioxide, alcohol and lactic acid are produced. Of great importance is adenosine-triphosphorus acid (ATP), which is synthesized by the mitochondria into adenosine-diphosphorus acid (ADP) and orthophosphate. Complicated chemical compounds are of great importance as reaction catalyst.
Stimulation of the vesicular respiration, especially a stimulation of the ATP production by cells, is used therapeutically, preferably for the promotion of strong use of cell energy in the healing processes and by reduction of weight, healing of wounds and a reduction of pain sensitivity due to an illness or weakness caused by hypopolarization or depolarization of the cell membrane. In general, weakening of cells caused by an increase of vesicular respiration due to stress, illness or by old age can be counteracted. In order to achieve stimulation of the mitochondria through optical radiation, two conditions must be fulfilled. The radiation must be of appropriate wavelengths in order to be effective, and a pulse frequency must be chosen to penetrate to an appropriate tissue depth without causing tissue damage or pain.
A device is known (Patent DE-U-8813852/Normed, E. Larsen). which uses infrared radiation for the photodynamic stimulation of energy in living cells, cells at the surface of the skin and especially cells lying deeper down. The device consists of a supply and control mechanism and an applicator on which infrared radiation from 900 nm (1 nm=1 nanometer) radiating IR (infrared) semiconductor diodes are mounted with reflectors for the bundling of the IR radiation from the applicator. In this known device, a generator containing a controller mechanism supplies the semiconductor diodes with current pulses of a certain frequency within the range of 500–5000 Hz. A disadvantage of the known device is that the semiconductor diodes during use tend to overheat, which causes a decrease in the effectiveness of the device. The known device therefore does not deliver a constant effect during use. Another disadvantage is that only infrared radiation within a range of 900 nm is available, while other wavelengths may be called for to achieve cell stimulation.
Light is used for bonding and hardening of plastic composite filling materials containing an agent which is photosensitive to light of 400–500 nm. wavelength (blue light). Worldwide, there are many producers of such materials (e.g., 3M Corporation, which also manufactures appropriate lamps). Information on these materials and lamps may be found on the Internet.
Well known in the art is a halogen lamp with a lamp housing including a reflector and a filter to obtain light output in the 400–500 nm. range (blue light). The housing also contains a fan to cool the lamp and filter but practical considerations concerning the size of the housing and the capacity of the fan typically result in insufficient cooling during operation, which causes the light output to vary. This can result in improper hardening, and perhaps also shrinking, of the fillings. Further, the lamps and filters must be replaced frequently. And, the apparatus is bulky and thus unwieldy in use.
The halogen apparatus has in the past been used mainly for setting plastic fillings in front teeth where relatively small amounts of filling material are used, and access is relatively easy. Recently however, there has been speculation that so-called silver fillings (actually mercury based) which have traditionally been used in the larger teeth may pose health risks, and many patients are requesting plastic fillings instead. Fillings in the larger teeth require much more filling material, and thus much more light dosage in order to harden properly without shrinkage, than in front teeth. The difficulties of using the unwieldy halogen apparatus are thereby exacerbated. For example, operating them at higher output results in temperature fluctuation, which in turn results in fluctuation of the light intensity which may result in improper hardening, and perhaps even shrinkage, of the fillings. Also, the lamps will have to be replaced more often.
In the field of dermatology, light is used as a stand-alone therapy for wounds, leg ulcers, eczema, burns, etc., and as such is used to stimulate tissue directly. Techniques are known for introducing agents for altering the light absorbing qualities of tissue to enhance the effect of light (for example, U.S. Pat. No. 5,226,907 to Tankovich teaches contamination of hair follicles with a dark particulate material to enhance light-induced heating in the follicles for hair removal).
Treatments have included the application of substances such as photofrin, 5-aminolevulan acid, hermatoporphyrin, verteporfin, chlorins, phthalodyanines, phenothiazine, and benzoporphyrin-derivative monoacid-A (ATMPn) onto or into tissue for healing solar keratoses, basal cell carcinoma, melanomas, etc. Such substances are known as “biopharmaceuticals” and treatment with these substances has been called biopharmaceutical therapy. Therapy involving the application of biopharmaceuticals and their subsequent activation by light after they have been absorbed into tissue has been called photodynamic therapy (PDT).
PDT has been used successfully in the treatment of internal inoperable cancers. A biopharmaceutical (specifically, hermatoporphyrin) is injected into the tumor tissue, and an optical method known as photodynamic diagnostic (PDD) is used to determine when the biopharmaceutical has been absorbed by the entire tumor. Then the tumor tissue is irradiated with light typical for a dye laser, which activates the photosensitive reactors in the hermatoporphyrin, whereby singlet oxygen is liberated. Singlet oxygen is toxic to protein and phosphorlipids in the tumor tissue, whereby the tumor is destroyed without destroying the surrounding tissue.
For treatment of skin keratosis (pre-cancerous tissue), trials with, for example, 5-aminolevulinic acid have shown that it can be used effectively in PDT if introduced into oil in a water suspension which is then applied to skin keratosis and then irradiated with a light source. A fast and cosmetically perfect healing has been attained with a very low rate of recurrence compared to conventional treatments, such as cryotherapy.
In view of these favorable test results, it is anticipated that pharmaceutical companies will be marketing the next generations of PDT chemicals in convenient forms, such as creams, suspensions, sprays, etc.
The light source typically used to irradiate PDT chemicals is commonly known as the surgical laser, a solid-state laser which is bulky, and which is expensive both to purchase and to operate. Surgical lasers are designed primarily for cutting, i.e., they output very high energy in a very small spot, and are thus difficult to adapt to the requirement to irradiate a more generalized area for PDT. Further, they generally radiate at a single wavelength. Radiation at several wavelengths is desirable in PDT, for several reasons: a single wavelength may cause the patient to experience burning pain in the tissue adjoining the tissue under treatment; some photosensitive chemicals respond to two different wavelengths; and, some pigmented melanomas do not respond to visible radiation due to absorption in the pigment (typically melanin), and must be irradiated with near-infrared light.
Common dermatological diseases like acne, warts, and onychomycosis (nail fungus) can successfully be treated with light as a stand-alone treatment, but recent work indicates that treatments using PDT (with ALA/5-aminolevulanic acid) give excellent results with only two or three treatments.
In a recent pilot study using PDT to treat acne, the cosmetic results were excellent, and oil gland activity which causes acne, and the resultant inflammation, were reduced for as much as twenty weeks after a series of PDT treatments. (The PDT treatments precipitated immediate but short-term inflammatory reactions.) In general the photodynamic stimulation used in the physiotherapy is producing very good results, but in the area of long-term chronic diseases such as gout, arthritis, etc. there is often a need for many treatments, as many as 12–20 treatments spaced over a period of time. Also, initial phases of such treatment often cause reactions, which in turn cause pain and discomfort.